title: Imaging and pharmacokinetics of (64)Cu-DOTA-HB22.7 administered by intravenous, intraperitoneal, or subcutaneous injection to mice bearing non-Hodgkin's lymphoma xenografts.
abstract: OBJECTIVE
  The aim of the study is to compare the tumor-specific targeting, pharmacokinetics, and biodistribution of (64)Cu-DOTA-HB22.7 when administered to xenograft-bearing mice intravenously (IV), intraperitoneally (IP), and subcutaneously (SQ).
  
  
  METHODS
  Mice bearing human non-Hodgkin's lymphoma (NHL) xenografts were injected IV, IP, or SQ with (64)Cu-DOTA-HB22.7. Xenograft targeting was evaluated by micro positron emission tomography (microPET) and confirmed by organ biodistribution studies. Blood measurements of (64)Cu were performed to determine the pharmacokinetics and clearance of (64)Cu-DOTA-HB22.7.
  
  
  RESULTS
  (64)Cu-DOTA-HB22.7 demonstrated equivalent tumor targeting within 24-48 h, regardless of the route of administration. Organ biodistribution confirmed tumor-specific targeting. Blood pharmacokinetics demonstrated that (64)Cu-DOTA-HB22.7 accessed the bloodstream after IP and SQ administration to a similar degree as IV administration, albeit at a slower rate.
  
  
  CONCLUSIONS
  These findings establish (64)Cu-DOTA-HB22.7 as a potential radioimmunotherapeutic and/or NHL-specific imaging agent. These findings provide evidence that IP and SQ administration can achieve results equivalent to IV administration and may lead to more efficient, reproducible treatment plans for antibody-based therapeutics.
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, University of California, Davis Cancer Center, Davis, CA, USA.
authors.forename: Shiloh M
authors.initials: SM
authors.lastname: Martin
authors.forename: Robert T
authors.initials: RT
authors.lastname: O'Donnell
authors.forename: David L
authors.initials: DL
authors.lastname: Kukis
authors.forename: Craig K
authors.initials: CK
authors.lastname: Abbey
authors.forename: Hayes
authors.initials: H
authors.lastname: McKnight
authors.forename: Julie L
authors.initials: JL
authors.lastname: Sutcliffe
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Tuscano
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003301:Copper Radioisotopes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D005434:Flow Cytometry; D018796:Immunoconjugates / Q000008:administration & dosage / Q000493:pharmacokinetics; D007267:Injections; D008228:Lymphoma, Non-Hodgkin / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D013388:Succinimides / Q000008:administration & dosage / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D003301:Copper Radioisotopes; C502492:DOTA-NHS; D018796:Immunoconjugates; D019275:Radiopharmaceuticals; D013388:Succinimides